The AIDS virus pol gene encodes three proteins that function as enzymes: a protease; the viral DNA polymerase (reverse transcriptase); and an endonuclease/integrase. Each of these proteins is a potential target for an inhibitor that could block virus replication. These proteins will be purified from bacteria that have been engineered to overproduce the AIDS virus pol gene products. These proteins will be used in biochemical analysis and for crystallization. The bacterial expression system will also be used for genetic analysis of the pol gene. Protein crystals formed in the presence and absence of specific ligands (including azido- thymidine triphosphate) will be used to determine the x-ray crystal structure using the isomorphous replacement method. The combined information obtained from genetic and biochemical studies and structure determination will provide a detailed understanding of each of these proteins and provide a basis for rational drug design.